Treatment with Volanesorsen Shows Efficacy in Patients with FCS

Treatment with Volanesorsen Shows Efficacy in Patients with FCS

By Krista Rossi

At the National Lipid Association (NLA) Scientific Sessions in Las Vegas, NV this morning, Akcea presented results from its ReFOCUS study, which evaluated the burden of illness and quality of life (QoL) in patients suffering from familial chylomicronemia syndrome (FCS), both before and during treatment with the company’s investigational drug, volanesorsen.

While limitations (such as a small sample size, retrospective study design, and potential influence of recall bias in patient-reported outcomes) apply to the study, the results suggest volanesorsen may be an effective FCS treatment for symptom management. Since there are currently no approved therapies from the US Food and Drug Administration (FDA) for FCS, these positive results bare significance.

FCS is a rare genetic disorder characterized by reduced or absent lipoprotein lipase activity, resulting in the accumulation of triglycerides (TGs) in the blood. Recurrent and potentially fatal acute pancreatitis (AP) are the most severe clinical consequences of FCS. As a result, FCS patients are restricted to an extremely low-fat diet (≤20 g daily), abstinence from alcohol, and simple-carbohydrate intake.

Volanesorsen is a second-generation antisense oligonucleotide that inhibits the production of apolipoprotein C-III and causes a reduction in plasma TG levels. It is currently under investigation in Phase 3 clinical trials.

Patient demographics in the ReFOCUS study included a 73% female population with a median age of 51 and a median age at FCS diagnosis of 24. Sixty-eight percent had a family history of FCS, and the median number of physicians before diagnosis per patient was 3. Fifty-five percent received misdiagnoses previously.

Primary measures included self-reported patient outcomes on approaches for FCS symptom management, the effectiveness of managing symptoms, the number of symptoms experienced, the reduction of symptoms experienced, experiences with AP, impact of FCS on personal, social, and professional life, interference of FCS with work/school attendance and responsibilities, and interference of FCS with mental/emotional wellbeing.

After 3 months of volanesorsen treatment, patients reported an overall 39% increase in effectiveness to approaches for managing FCS, a 44% mean improvement in the number of symptoms experienced, and a 66% improvement from baseline in the number of respondents who experienced 10 symptoms. Patients also experienced an 88% improvement of pancreatic pain, a 100% improvement in the incidence of steatorrhea, and an 80% in constant worry over pain/pancreatic attacks.

In addition, the percentage of FCS patients who did not experience AP increased from 77% to 95%, the impact of FCS on personal, social, and professional life improved by 22%, the interference of FCS with work/school attendance and responsibilities improved by 42%, and the emotional wellbeing of FCS patients improved by 40%.

The ReFOCUS study results conclude that volanesorsen has potential to positively impact FCS patients’ QoL across multiple domains. Patient reports of easier dietary management and more effective symptom control with volanesorsen treatment, and improvememnt in physical, emotional, and cognitive symptoms further add to the drug’s potential.

For more from the NLA Sessions, follow Rare Disease Report on Facebook and Twitter.

References:

Arca M, et al. Assessing the Disease Burden Among Patients with Familial Chylomicronemia Syndrome (FCS) on Volanesorsen: Results of the ReFOCUS Study. Presented at: 2018 National Lipid Association (NLA) Scientific Sessions; April 26-29, 2018; Las Vegas, Nevada.